Magnetoelectric response fiber membrane as well as preparation method and application thereof

Abstract

The invention discloses a magnetoelectric response fiber membrane as well as a preparation method and application thereof, and relates to the technical field of magnetoelectric response materials. The preparation method of the magnetoelectric response fiber membrane comprises the following steps: mixing and dissolving magnetic particles and a piezoelectric polymer in an organic solvent, and carrying out electrostatic spinning to obtain the magnetoelectric response fiber membrane, the polarization of the piezoelectric polymer is completed in the electrostatic spinning process. The piezoelectric polymer and the magnetic particles are spun into the magnetoelectric response fiber membrane through the electrostatic spinning technology, the tedious independent polarization step of the piezoelectric polymer is reduced, the obtained magnetoelectric response fiber membrane can simulate a natural extracellular matrix (ECM) from the structure, magnetostriction and piezoelectric properties are combined together, and the magnetoelectric response fiber membrane is prepared. The magnetic field can be directly used for controlling the magnetic particles to drive the piezoelectric polymer to deform, so that electrical activity is generated, and a micro-current environment is simulated.

Description

Technical Field

[0001] The present invention relates to the technical field of magnetoelectric response materials, and in particular to a magnetoelectric response fiber membrane and a preparation method and application thereof. Background Art

[0002] Magnetoelectric responsive materials are materials that combine the effects of piezoelectric materials and magnetostrictive materials. They are special materials with both magnetic and electrical properties. Piezoelectric materials are intelligent materials that can respond to electrical activity generated by tiny deformations, so there is no need to apply external sources of electrical stimulation or electrode implantation. Various piezoelectric materials have been used in different tissue repair applications, especially in bone repair and nerve repair. The charge caused by mechanical stress can enhance bone formation; in neural tissue engineering, electric pulses can stimulate the directional growth of neurites to fill the gaps in neural tissue damage. However, when it comes to skull repair, some patients are difficult to provide the stress required to stimulate the piezoelectric effect due to their special position (such as skull, dura mater), so the piezoelectric effect of the stent is difficult to play, and effective stimulation of the damaged part cannot be achieved. In addition, piezoelectric materials are mainly divided into organic piezoelectric materials and inorganic piezoelectric materials. Inorganic piezoelectric materials have strong piezoelectricity and high dielectric constant, but molding requires high-temperature sintering and has relatively strong rigidity, while organic piezoelectric materials have a high polarization voltage, so the development of piezoelectric materials is limited. Magnetostrictive materials, as a new type of smart material, can move and rotate between magnetic domains in response to external magnetic fields, causing the material to stretch and deform in length and volume. This shape change is expected to provide a stress source for the activation of piezoelectric materials by inducing their domain reversal. Therefore, the use of magnetoelectric responsive materials formed by combining magnetostrictive materials with piezoelectric materials is expected to solve the problem of difficult polarization of piezoelectric materials and difficulty in exerting the piezoelectric effect.

[0003] The prior art provides a CoFe2O4 / PVDF composite bone scaffold, wherein CoFe2O4 / PVDF is a magnetoelectric responsive material, but the preparation steps of the composite bone scaffold are complicated, requiring laser sintering to form first and then further polarization. In addition, due to the presence of pores in the formed composite bone scaffold, it is very easy to be broken down under a high-voltage electric field, resulting in polarization failure, or the polarization voltage needs to be reduced, resulting in incomplete polarization, which affects the piezoelectric properties of the material. In scenarios where it is difficult to provide the stress required to excite the piezoelectric effect, the piezoelectric effect is still not ideal, and it is difficult to realize its application in nerve repair. Summary of the invention

[0004] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, the purpose of the present invention is to provide a method for preparing a magnetoelectric responsive fiber membrane, which uses an electrostatic spinning process to obtain a magnetoelectric responsive fiber membrane with piezoelectric and magnetostrictive effects, and polarization can be performed during electrostatic spinning without affecting the piezoelectric properties.

[0005] A second aspect of the present invention provides a magnetoelectric responsive fiber membrane obtained by a method for preparing a magnetoelectric responsive fiber membrane.

[0006] The third aspect of the present invention provides an application of a magnetoelectric responsive fiber membrane.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] The first aspect of the present invention is to provide a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0009] The magnetic particles and the piezoelectric polymer are mixed and dissolved in an organic solvent, and the magnetoelectric responsive fiber membrane is obtained by electrostatic spinning; the polarization of the piezoelectric polymer is simultaneously completed during the electrostatic spinning process.

[0010] Electrospinning is a special fiber manufacturing process in which a polymer solution or melt is jet-spun in a strong electric field. Under the action of the electric field, the droplet at the needle tip changes from a spherical shape to a conical shape (i.e., a "Taylor cone"), and fiber filaments are extended from the tip of the cone. The fiber membrane formed by electrospinning has a unique fiber structure that can simulate the structure and biological function of the natural extracellular matrix and can play a role in tissue engineering. The present invention adopts an electrospinning process to produce polymer filaments of nanometer-scale diameter, and the formed fiber membrane can imitate the characteristics of the extracellular matrix, so a nanofiber scaffold highly similar to the natural extracellular matrix architecture can be formed.

[0011] It should be noted that in the preparation method of the present invention, during the electrospinning process, since the solvent evaporates when the Taylor cone is formed to pull the filamentary fiber to the collector, the formed fiber is collected on the collector to directly form a fiber membrane.

[0012] The magnetoelectric responsive fiber membrane prepared by the present invention has good piezoelectric and magnetostrictive effects, combines magnetostriction with piezoelectric properties, uses a magnetic field to control the magnetoelectric material to drive the deformation of the piezoelectric material to generate electrical activity, simulates a microcurrent environment, and can use the electrospinning electric field to simultaneously achieve polarization during the electrospinning process, without the need for separate polarization, and combines molding and polarization into one step, simplifying the process steps.

[0013] In some embodiments of the present invention, the magnetic particles are magnetic particles modified by a surface modifier.

[0014] The modified magnetic particles have better dispersibility than the unmodified ones, less coagulation effect, and can be more evenly distributed on the fibers.

[0015] In some embodiments of the present invention, the surface modifier includes at least one of a silane coupling agent and dopamine hydrochloride.

[0016] In some specific embodiments of the present invention, the surface modifier includes at least one of γ-aminopropyltriethoxysilane (KH-550) and dopamine hydrochloride.

[0017] In some specific embodiments of the present invention, the mass concentration of the surface modifier is 1-2%.

[0018] In some embodiments of the present invention, the particle size of the magnetic particles is 10 to 200 nm.

[0019] In some embodiments of the present invention, the particle size of the magnetic particles is 10-100 nm.

[0020] The present invention further limits the particle size of the magnetic particles, which are smaller than the size of the nanofibers obtained by electrospinning (the single fiber diameter is 500nm to 5μm), and can be better fully or partially wrapped by the nanofibers, thereby more fully utilizing the magnetostrictive effect to transfer strain to the piezoelectric polymer.

[0021] In some embodiments of the present invention, the magnetic particles and the piezoelectric polymer are mixed and dissolved in an organic solvent to form a precursor solution; the mass fraction of the precursor solution is 5 to 35%.

[0022] The present invention further limits the mass fraction of the precursor solution, which can better ensure that uniform nanofibers can be obtained during the electrospinning process and avoid the formation of beads or coarse fibers.

[0023] In some embodiments of the present invention, the mass fraction of the precursor solution is 5-25%.

[0024] In some specific embodiments of the present invention, the mass fraction of the precursor solution is 10-25%.

[0025] In some examples of the present invention, the mass fraction of the precursor solution is 8-15%.

[0026] In some examples of the present invention, the mass fraction of the precursor solution is 10-15%.

[0027] In some embodiments of the present invention, in the precursor solution, the mass ratio of the piezoelectric polymer to the magnetic particles is (5-50):1.

[0028] In some specific embodiments of the present invention, in the precursor solution, the mass ratio of the piezoelectric polymer to the magnetic particles is (9-49):1.

[0029] In some specific embodiments of the present invention, in the precursor solution, the mass ratio of the piezoelectric polymer to the magnetic particles is (5-25):1.

[0030] In some specific embodiments of the present invention, in some specific embodiments of the present invention, in the precursor solution, the mass ratio of the piezoelectric polymer to the magnetic particles is (8-20):1.

[0031] The content of magnetic particles and piezoelectric polymers is further limited. On the one hand, the magnetic particles are needed to provide a magnetostrictive effect. However, when the content is high, the density of the magnetic particles is large and they are prone to stratification during electrospinning. On the other hand, in the present invention, the magnetic particles also need to be evenly dispersed in the precursor solution to avoid the problem of stratification of the solution and the magnetic particles. Adjusting the proportion of the magnetic particles is also beneficial to their dispersion in the precursor solution.

[0032] In some embodiments of the present invention, the electrospinning conditions satisfy at least one of the following a) to d):

[0033] a) Positive high voltage is 10~30kV; negative high voltage is -1~-3kV;

[0034] b) The collector shaft speed is 500-6000 rpm;

[0035] c) The distance between the needle and the collector is 12 to 20 cm;

[0036] d) The advancement speed is 0.01~6mL / h.

[0037] By controlling the electrospinning parameters, especially the collector shaft speed, controllable directional fiber orientation can be achieved, and at the application end, it can achieve directional induction of neural cell and osteoblast migration and promote differentiation.

[0038] In some embodiments of the present invention, the positive high voltage is 15-20 kV.

[0039] In some embodiments of the present invention, the collector shaft has a rotation speed of 500 to 3000 rpm.

[0040] In some embodiments of the present invention, the collector shaft has a rotation speed of 1000 to 3000 rpm.

[0041] In some embodiments of the present invention, the advancement speed is 0.5-1 mL / h.

[0042] In some embodiments of the present invention, the organic solvent includes at least two of acetone, formic acid, DMF (N,N-dimethylformamide), dichloromethane, chloroform, and tetrahydrofuran.

[0043] Different piezoelectric polymers need different organic solvents to dissolve in order to form a solution, but electrospinning also requires a suitable solvent to enable it to dry quickly from spinning to collection to avoid fusion between the silks in the collector. Therefore, at least two organic solvents are required for preparation. Solvents with different boiling points are prepared according to the boiling point of the good solvent of the piezoelectric polymer, and at the same time, the precipitation of the piezoelectric polymer is avoided. For example, PVDF-TrFE is soluble in DMF, but the boiling point of DMF is above 150°C and it is difficult to volatilize, so its volatilization rate can be adjusted with acetone (boiling point above 60°C), and since PVDF-TrFE is insoluble in acetone, the acetone content is low to avoid the precipitation of PVDF-TrFE.

[0044] In some embodiments of the present invention, the organic solvent comprises at least one of the three combinations of DMF and acetone, DMF and tetrahydrofuran, and DMF and chloroform.

[0045] In some embodiments of the present invention, the volume ratio of the two components in the organic solvent is (4-6): (6-4).

[0046] In some embodiments of the present invention, the magnetic particles include at least one of cobalt ferrite, ferrosoferric oxide, and superparamagnetic iron oxide.

[0047] In some embodiments of the present invention, the piezoelectric polymer includes at least one of PHB, PHBV, PLA, PVDF, PVDF-TrFE, and odd-numbered PA.

[0048] In some embodiments of the present invention, in the magnetoelectric responsive fiber membrane, the mass percentage of the magnetic particles is 2-20%.

[0049] In some embodiments of the present invention, in the magnetoelectric responsive fiber membrane, the mass percentage of the magnetic particles is 2-10%, for example, 2%, 5%, 8% or 10%.

[0050] The preparation method provided in the first aspect of the present invention uses piezoelectric polymer and magnetic particles as raw materials, introduces magnetic particles, and uses a magnetic field to control the magnetic particles to drive the deformation of the piezoelectric polymer to generate electrical activity during application. In addition, the present invention can use the electrospinning electric field to polarize the piezoelectric polymer during electrospinning through the electrospinning technology, and the polarization voltage is low. By further adjusting the rotation speed of the collector, magnetoelectric response fiber membranes with different degrees of orientation can be prepared.

[0051] The second aspect of the present invention provides a magnetoelectric responsive fiber membrane prepared by the preparation method described in the first aspect of the present invention.

[0052] In some embodiments of the present invention, the piezoelectric coefficient of the magnetoelectric responsive fiber membrane is 45-55p / CN.

[0053] The third aspect of the present invention provides an application of the magnetoelectric responsive fiber membrane described in the second aspect of the present invention in the field of biomedical materials.

[0054] The magnetoelectric responsive fiber membrane of the present invention effectively combines the piezoelectric response of piezoelectric polymers and the magnetostrictive effect of magnetic materials, and solves the problem of difficult polarization of piezoelectric polymers by utilizing electrospinning molding. The fiber orientation can be controlled by controlling electrospinning process parameters. The preparation process is simple and the cost is low. It has important promotion and application value and is more suitable as a biomedical material, especially for bone repair (such as brain bone defect repair) and nerve repair.

[0055] In some embodiments of the present invention, the biomedical material comprises a bone repair material or a nerve repair material.

[0056] In some embodiments of the invention, the bone repair comprises skull repair.

[0057] The repair process of skull and nerve has the problem of not being able to bear pressure, and piezoelectric polymers generally need pressure to produce deformation to generate electrical signals when in use, so it is difficult to play an effect in skull and nerve repair. The polarization voltage of the magnetoelectric response material of the present invention is low, and the electric field in the electrostatic spinning process can be used to complete polarization at the same time during electrostatic spinning, with excellent piezoelectric and magnetostrictive effects, and can act on the bone guide membrane of the skull defect site, and the electrical signal generated by piezoelectricity has also been proven to promote osteogenesis and nerve repair. In addition, the magnetoelectric response fiber membrane of the present invention is a filamentous fiber membrane with high porosity, and better simulates the structure of the extracellular matrix, making it more conducive to the differentiation of osteoblasts.

[0058] Compared with the prior art, the present invention has the following beneficial effects:

[0059] (1) The present invention uses electrostatic spinning technology to weave piezoelectric polymers and magnetic particles into magnetoelectric responsive fiber membranes. The magnetoelectric responsive fiber membranes can structurally mimic the natural extracellular matrix (ECM) and combine magnetostriction with piezoelectric properties. The magnetic field can be directly used to control the magnetic particles to drive the deformation of the piezoelectric polymer, thereby generating electrical activity and simulating a microcurrent environment. In addition, the preparation method of the present invention also reduces the cumbersome individual polarization steps of the piezoelectric polymer, and the preparation process is simple, easy to control, highly operable, low cost, and suitable for industrial mass production.

[0060] (2) The magnetoelectric responsive fiber membrane prepared by the present invention can be widely used in the field of biomedical materials, and is particularly suitable for the repair of bone defects such as the skull that are not suitable for pressure or the repair of nerve-related parts. The magnetostrictive effect is used to induce the piezoelectric effect without applying additional pressure, thereby generating microcurrent to stimulate the nerves or bone defects, thereby achieving the repair function. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 The surface SEM images of the fiber membranes of Examples 1 to 2 and Comparative Example 2 are shown; wherein: Figure 1 a), b), and c) are SEM images of the fiber membranes of Example 1, Example 2, and Comparative Example 2, respectively.

[0062] Figure 2 : is a comparison chart of the piezoelectric test results of the fiber membranes of Example 1 and Comparative Example 1; wherein, Figure 2 a), Figure 2 d) is the amplitude diagram of Example 1 and Comparative Example 1, Figure 2 b) Figure 2 e) is the phase diagram of Example 1 and Comparative Example 1, Figure 2 c) Figure 2 f) is the butterfly curve of Example 1 and Comparative Example 1.

[0063] Figure 3 It is a comparison chart of the magnetostrictive performance test results of the magnetoelectric responsive fiber membranes of Examples 1 to 4.

[0064] Figure 4 The surface SEM images of the fiber membranes obtained at different collector shaft speeds in Comparative Examples 3 to 4; Figure 4 a) is the morphology of the electrospinning membrane at a low speed of 500 rpm. Figure 4 b) is the scanning electron microscope morphology at a high speed of 3000 rpm. Figure 4 c) Rat bone marrow mesenchymal stem cells Figure 4 a) Scanning electron microscopy image of the fiber membrane after 7 days of culture. Figure 4 d) Rat bone marrow mesenchymal stem cells Figure 4 b) Scanning electron micrograph of the fiber membrane after 7 days of culture.

[0065] Figure 5 Surface SEM images of fiber membranes obtained with different precursor solution concentrations in Comparative Example 5.

[0066] Figure 6 It is a comparison chart of the magnetoelectric coupling coefficient test results of the fiber membranes of Example 1 and Comparative Example 2; wherein, Figure 6 a is the graph of magnetoelectric coupling changing with frequency, Figure 6 b is the graph of magnetoelectric coupling changing with magnetic field.

[0067] Figure 7 This is a comparison chart of the 7D cell proliferation live-dead fluorescence effects of the fiber membranes of Example 2 and Comparative Example 1.

[0068] Figure 8 This is a comparison diagram of the 7D cytoskeleton staining fluorescence effects of the fiber membranes of Example 2 and Comparative Example 1.

[0069] Fig. 9 7D and 14D osteogenic differentiation SEM images of Example 2 and Comparative Example 1; wherein, Fig. 9 a), Fig. 9 b) is the 7D osteogenic differentiation SEM image of Comparative Example 1 and Example 2, Fig. 9 c) Fig. 9 d) is the SEM image of 14D osteogenic differentiation of comparative example and Example 2.

[0070] Fig.10 The figure is a comparison chart of the effects of Example 2 and Comparative Example 1 on Schwann cell gene expression. DETAILED DESCRIPTION

[0071] The present invention is further described in detail below by specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources or can be obtained by prior art methods. Unless otherwise specified, the experiments or test methods are conventional methods in the art.

[0072] The magnetic particles used in the following examples and comparative examples of the present invention are all selected from magnetic nanoparticles with a particle diameter of less than 100 nm.

[0073] Example 1

[0074] This embodiment provides a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0075] 0.9 g PVDF-TrFE and 0.1 g modified cobalt ferrite (CFO) were added to a mixed solution of 8 mL DMF (N,N-dimethylformamide) and acetone (volume ratio 6:4), stirred for 10 min, ultrasonically dispersed for 2 h, and stirred for another 10 min to obtain a PVDF-TrFE / CFO composite precursor solution. The prepared precursor solution was placed in a 10 mL syringe, with a positive pressure of 18 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 0.5 mL / h, and the distance between the needle and the collector was set to 15 cm for electrospinning to obtain a magnetoelectric responsive fiber membrane.

[0076] The surface modification method of CFO comprises the following steps: weighing 2g of nano cobalt ferrite (CFO) and adding it into an ethanol solution of KH550 with a mass fraction of 1%, stirring overnight, centrifuging and washing three times, drying in an oven at 50°C overnight, grinding and sieving to obtain dry modified CFO.

[0077] Example 2

[0078] This embodiment provides a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0079] 0.95 g PVDF-TrFE and 0.05 g modified CFO were added to a mixed solution of 8 mL DMF and acetone (volume ratio of 5:5), stirred for 10 min, ultrasonically dispersed for 2 h, and stirred for another 10 min to obtain a PVDF-TrFE / CFO composite precursor solution. The prepared precursor solution was placed in a 10 mL syringe, with a positive pressure of 18 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 0.5 mL / h, and the distance between the needle and the collector was set to 15 cm for electrospinning to obtain a magnetoelectric responsive fiber membrane.

[0080] The surface modification method of CFO comprises the following steps: weighing 2g CFO and adding it into an ethanol solution of dopamine hydrochloride with a mass fraction of 1%, stirring overnight, centrifugally washing three times, drying in an oven at 50°C overnight, grinding and sieving to obtain dry modified CFO.

[0081] Example 3

[0082] This embodiment provides a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0083] 0.95 g PLLA and 0.05 g modified CFO were added to a mixed solution of 8 mL DMF and THF (tetrahydrofuran) (volume ratio of 4:5), stirred for 10 min, ultrasonically dispersed for 2 h, and stirred for another 10 min to obtain a PLLA / CFO composite precursor solution. The prepared precursor solution was placed in a 10 mL syringe, with a positive pressure of 20 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 1 mL / h, and the distance between the needle and the collector was set to 15 cm for electrospinning to obtain a magnetoelectric responsive fiber membrane.

[0084] The surface modification method of CFO comprises the following steps: weighing 2g of nano cobalt ferrite (CFO) and adding it into an ethanol solution of KH550 with a mass fraction of 1%, stirring overnight, centrifuging and washing three times, drying in an oven at 50°C overnight, grinding and sieving to obtain dry modified CFO.

[0085] Example 4

[0086] This embodiment provides a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0087] 0.9 g PLLA and 0.1 g modified Fe3O4 were added to 12 mL of a mixed solution of DMF and THF (volume ratio 6:4), stirred for 10 min, ultrasonically dispersed for 2 h, and stirred for another 10 min to obtain a PVDF / CFO composite precursor solution. The prepared precursor solution was placed in a 10 mL syringe, with a positive pressure of 18 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 1 mLh, and the distance between the needle and the collector was set to 10 cm for electrospinning to obtain a magnetoelectric responsive fiber membrane.

[0088] The surface modification method of Fe3O4 includes the following steps: weighing 2g of Fe3O4 nanoparticles, adding them into a 1% dopamine hydrochloride ethanol solution, stirring overnight, centrifuging and washing three times, drying in an oven at 50°C overnight, grinding and sieving to obtain dry modified Fe3O4.

[0089] Example 5

[0090] This embodiment provides a method for preparing a magnetoelectric responsive fiber membrane, comprising the following steps:

[0091] 0.98g PHBV and 0.02g modified Fe3O4 were added to a mixed solution of 10mL chloroform and DMF (volume ratio 6:4), stirred for 10min, ultrasonically dispersed for 2h, and stirred for another 10min to obtain a PVDF / CFO composite precursor solution. The prepared precursor solution was placed in a 10mL syringe, with a positive pressure of 15kV and a negative pressure of -1.8kV. The collector was wrapped with aluminum foil, the drum speed was set to 1500r / min, the syringe injection rate was 1mL / h, and the distance between the needle and the collector was set to 12cm for electrospinning to obtain a magnetoelectric responsive fiber membrane.

[0092] The surface modification method of Fe3O4 includes the following steps: weighing 2g of Fe3O4 nanoparticles and adding them into a 1% by mass dopamine hydrochloride ethanol solution, stirring overnight, centrifuging and washing three times, drying in a 50°C oven overnight, grinding and sieving to obtain dry modified Fe3O4.

[0093] Comparative Example 1

[0094] Comparative Example 1 provides a method for preparing a fiber membrane, comprising the following steps:

[0095] 1 g of PVDF-TrFE was added to a mixed solution of 8 mL of DMF and acetone (volume ratio 6:4), stirred for 10 min, and ultrasonically dispersed for 2 h to obtain a PVDF-TrFE spinning solution. The prepared spinning solution was placed in a 10 mL syringe, with a positive pressure of 18 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 0.5 mL / h, the distance between the needle and the collector was set to 15 cm, and a fiber membrane was obtained by electrospinning.

[0096] Comparative Example 2

[0097] Comparative Example 2 provides a method for preparing a fiber membrane, comprising the following steps:

[0098] 0.9 g PVDF-TrFE and 0.1 g unmodified CFO were added to 8 mL of a mixed solution of DMF and acetone (volume ratio 6:4), stirred for 10 min, and ultrasonically dispersed for 2 h to obtain a PVDF-TrFE spinning solution. The prepared spinning solution was placed in a 10 mL syringe, with a positive pressure of 18 kV and a negative pressure of -2 kV. The collector was wrapped with aluminum foil, the drum speed was set to 2000 r / min, the syringe injection rate was 0.5 mL / h, the distance between the needle and the collector was set to 15 cm, and a fiber membrane was obtained by electrospinning.

[0099] Comparative Example 3

[0100] This comparative example provides a method for preparing a fiber membrane. The steps are the same as those of comparative example 1, except that the drum speed during the electrospinning process is a low speed of 500 rpm.

[0101] Comparative Example 4

[0102] This comparative example provides a method for preparing a fiber membrane. The steps are the same as those of comparative example 1, except that the drum speed is as high as 3000 rpm during the electrospinning process.

[0103] Comparative Example 5

[0104] This comparative example provides a method for preparing a fiber membrane, and the steps are the same as those of comparative example 1, except that the mass fractions of the spinning solution are different, corresponding to 10%, 15%, 20%, and 25%, respectively.

[0105] It should be noted that among Comparative Examples 1 to 5, Comparative Example 1 is the basic material, which is mainly used to study the influence of electrospinning parameters on the morphology of the fiber membrane, while excluding the interference of magnetic nanoparticles. For example, the mass fraction of the spinning solution in Comparative Example 5 is different. Because the mass fraction is different, the viscosity of the solution is also different. Therefore, if there are magnetic nanoparticles, they will be deposited at low concentrations, while the high concentration may not be deposited obviously due to the viscosity, and the medium concentration can be stably present for a long time after modification. Therefore, if magnetic nanoparticles are added, the above variables will exist, and the influence of spinning solutions with different mass fractions on the spinning morphology cannot be simply compared.

[0106] Performance Testing

[0107] The following are relevant performance tests on the above embodiments and comparative examples.

[0108] 1. Comparison of the effects before and after magnetic particle modification

[0109] Comparison of the coagulation effect of the magnetic particles in Examples 1 to 2 and Comparative Example 2 after the same electrospinning time, the results are as follows: Figure 1 As shown. Figure 1 It can be seen that the modified magnetic particles in Examples 1 and 2 are more evenly dispersed on the fibers, while in Comparative Example 2, large particles agglomerate, and at the same magnification in the field of view, there are fewer magnetic particles. This is because the unmodified magnetic particles precipitate during spinning, resulting in stratification in the pipeline. By comparing Comparative Example 2 and Example 2, which contain the same content of magnetic particles, it can also be seen that the unmodified magnetic particles are more likely to aggregate under the electric field and gravity, while the modified magnetic particles can be more evenly dispersed in the spinning solution (precursor solution), and finally more evenly distributed on the fibers, indicating that the modification has an improving effect on the dispersion of magnetic particles in the spinning solution and the magnetoelectric responsive fiber membrane.

[0110] 2. Piezoelectric test

[0111] The magnetoelectric responsive fiber membranes of Comparative Example 1 and Example 1 were subjected to PMF (Piezoelectric Response Force Microscope) test. The results are as follows: Figure 2 shown. Figure 2 The piezoelectric coefficient is shown in p / CN of about 50, which means that when the piezoelectric polymer is electrospun, the electric field polarizes the material at the same time, and it has piezoelectric properties, and the addition of magnetic particles has no effect on the piezoelectric coefficient.

[0112] 3. Magnetostrictive performance test

[0113] The magnetoelectric responsive fiber membranes of Examples 1 to 4 were tested for magnetostrictive properties, i.e., the magnetoelectric responsive fiber membranes were adsorbed by magnets, and successful adsorption indicated that the magnetostrictive properties were possessed. Figure 3 As shown, it is explained that the magnetoelectric responsive fiber membrane of the present invention has magnetostrictive properties.

[0114] 4. Comparison of different shaft speeds

[0115] Comparing the scanning electron microscope images of the fiber membranes of Comparative Examples 3 to 4, Figure 4 As shown, it can be seen that when the drum speed (i.e., the shaft speed) is different, the fiber orientation is different, which will lead to different cell spreading directions during subsequent bone promotion. Although no magnetic particles are added in Comparative Examples 3-4, the effect of the shaft speed on fiber growth can also be seen from the results of Comparative Examples 3-4.

[0116] 5. Comparison of concentrations of different precursor solutions

[0117] Comparing the scanning electron microscope images of the fiber membranes obtained with different spinning solution mass fractions in Comparative Example 5, Figure 5 shown. Figure 5 In the figure, A to D are SEM images of fiber membranes with mass fractions of 10%, 15%, 20%, and 25%, respectively (the scale bars are all 30 μm), and Figure 5 E is a fiber membrane with a spinning solution mass fraction of 15% ( Figure 5 B) Locally enlarged SEM image (scale bar is 10 μm), Figure 5 F is the local magnification of the fiber membrane with a spinning solution mass fraction of 15% ( Figure 5 E) is a statistical diagram of fiber size. It can be found that spinning at a lower concentration will form a beaded form, and as the concentration increases, the thin fibers become thicker. It should be noted that when the piezoelectric polymer changes, the optimal concentration is different. Combined with the results of Comparative Example 5, it can be expected that when magnetic particles are added, the mass fraction of the precursor solution is different, and the concentration range selected by the present invention is a concentration range suitable for most polymers.

[0118] 6. Magnetoelectric coupling coefficient of fiber membrane

[0119] The magnetoelectric coupling coefficient of the magnetoelectric responsive fiber membranes of Comparative Example 2 and Example 1 was measured in the frequency range of 0 to 1000 Hz. The results are as follows: Figure 6 (a) As shown. Obviously, as the frequency increases, the magnetoelectric coupling coefficient of the fiber membranes of Example 1 and Comparative Example 2 increases first and then decreases. The magnetoelectric coupling coefficient of the fiber membrane reaches a maximum value at a frequency of 1200 Hz.

[0120] Based on the above results, the magnetoelectric coupling coefficient of the fiber membrane of Example 1 and Comparative Example 2 was evaluated under a frequency of 1200 Hz, an AC magnetic field of 10 Oe, and a superimposed DC magnetic field of -10000 to +10000 Oe. The results are as follows: Figure 6 (b) As can be seen from the figure, the magnetoelectric coupling coefficient increases with the increase of the DC magnetic field. Compared with the magnetoelectric coupling coefficient of Comparative Example 2 using unmodified magnetic particles, the coupling coefficient of Example 1 is significantly improved ( Figure 6 b). It can be seen that the magnetoelectric responsive fiber film of the present invention can generate radio signals under the stimulation of an external magnetic field. When an external magnetic field is applied, the magnetic particles are magnetostrictively deformed, and the strain is transmitted to the piezoelectric polymer through interface coupling, resulting in a change in its surface polarization. Comparative Example 2 with the same magnetic particle content and Example 1 are subjected to an alternating magnetic field at the same magnetoelectric parameters. It can be seen that Example 1 has a better effect, mainly because the dispersion of the magnetic particles is improved and more magnetic particles are distributed on the piezoelectric fiber.

[0121] 7. Biocompatibility

[0122] (1) Osteogenesis: BMSCs (rat bone marrow mesenchymal stem cells) were seeded on the fiber membranes of Example 2 and Comparative Example 1 and stimulated in an alternating magnetic field for 10 min respectively, so that the magnetostriction of the material promoted the release of electrical signals by the piezoelectric material. Live and dead staining and cytoskeleton staining were performed after culturing in complete medium for 7 days (7D). The proliferation effect was observed under the conditions of no magnetic field and magnetic field (10 mT). The test results are as follows: Figure 7 and Figure 8 shown. Figure 7 The cell proliferation effect of Example 2 is significantly higher than that of Comparative Example 1, and no dead cells are found, indicating that the magnetoelectric responsive fiber membrane is beneficial to cell growth. Figure 8 The cytoskeleton staining of Example 2 and Comparative Example 1 showed that the cells were spread on the surface of the material after electrospinning to simulate the extracellular matrix. Example 2 grew along the fiber direction under the magnetic field.

[0123] The osteogenic differentiation of BMSCs on the surface of the material was observed using a scanning electron microscope after culturing with osteogenic induction solution for 7 days (7D) and 14 days (14D). Fig. 9 The 7D and 14D osteogenic differentiation SEM images of Example 2 and Comparative Example 1 show that the surface cells of the magnetoelectric responsive fiber membrane of Example 2 are calcified, and the content of calcium nodules is significantly higher than that of Comparative Example 1, indicating that the magnetoelectric responsive fiber membrane material of the present invention effectively promotes osteoblast differentiation.

[0124] (2) Neural expression: Rat Schwann cells were seeded on the fiber membranes of Example 2 and Comparative Example 1. After 24 hours, the cells were stimulated with an alternating magnetic field for 10 minutes. After 2 days, RNA was extracted for gene expression. The results are as follows: Fig.10 As shown, the expression of NGF gene, GDNF gene and GFAP gene in Example 1 is higher than that in Comparative Example 1, indicating that the magnetoelectric responsive fiber membrane of the present invention can promote neural expression.

[0125] The above test results show that the magnetoelectric responsive fiber membrane obtained by the preparation method of the present invention has excellent biocompatibility, internal magnetic particle dispersion, piezoelectric properties, and magnetostrictive properties, and the experimental results show that the magnetoelectric responsive fiber membrane can be used in the fields of bone repair and nerve repair.

[0126] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing a magnetoelectric responsive fiber membrane, characterized in that: The steps include: The magnetic particles and the piezoelectric polymer are mixed and dissolved in an organic solvent, and the magnetoelectric responsive fiber membrane is obtained by electrostatic spinning; the polarization of the piezoelectric polymer is simultaneously completed during the electrostatic spinning process.

2. The preparation method according to claim 1, characterized in that: The magnetic particles are magnetic particles modified by a surface modifier; And / or, the particle size of the magnetic particles is 10 to 200 nm.

3. The preparation method according to claim 2, characterized in that: The surface modifier includes at least one of a silane coupling agent and dopamine hydrochloride.

4. The preparation method according to claim 1 or 2, characterized in that: The magnetic particles and the piezoelectric polymer are mixed and dissolved in an organic solvent to form a precursor solution; the mass fraction of the precursor solution is 5-35%.

5. The preparation method according to claim 4, characterized in that: In the precursor solution, the mass ratio of the piezoelectric polymer to the magnetic particles is (5-50):

1.

6. The preparation method according to claim 1, characterized in that: The electrospinning conditions satisfy at least one of the following a) to d): a) Positive high voltage is 10~30kV; negative high voltage is -1~-3kV; b) The collector shaft speed is 500-6000 rpm; c) The distance between the needle and the collector is 12 to 20 cm; d) The advancement speed is 0.01~6mL / h.

7. The preparation method according to claim 1 or 2, characterized in that: The organic solvent comprises at least two of acetone, formic acid, DMF, dichloromethane, chloroform, and tetrahydrofuran; And / or, the magnetic particles include at least one of cobalt ferrite, ferroferric oxide, and superparamagnetic iron oxide; And / or, the piezoelectric polymer includes at least one of PHB, PHBV, PLA, PVDF, PVDF-TrFE, and odd-numbered PA.

8. A magnetoelectric responsive fiber membrane, characterized in that: The invention is prepared by the preparation method according to claims 1 to 7.

9. An application of the magnetoelectric responsive fiber membrane according to claim 8 in the field of biomedical materials.

10. The use according to claim 9, characterized in that: The biomedical material includes a bone repair material or a nerve repair material.

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